Forgue S T, Kari P, Barbhaiya R
Metabolism and Pharmacokinetics Department, Bristol-Myers Company, Syracuse, NY 13221-4755.
Drug Metab Dispos. 1987 Nov-Dec;15(6):808-15.
Cefepime (BMY-28142), 7-[alpha-(2-aminothiazol-4-yl)-alpha-(Z)-methoximin oacetamido] -3-[(1-methyl-1-pyrrolidino)-methyl]-3-cephem-4-carboxylate is a potent cephalosporin that is unique in having a quaternized N-methylpyrrolidino side chain. Degradation of the beta-lactam ring can result in release of N-methylpyrrolidine (NMP), an alicyclic tertiary amine. After iv bolus administration of [methyl-14C]NMP, most radioactivity in the urine of rats and a dog was present as a polar, nonextractable metabolite, which was isolated and identified as NMP N-oxide. A minor urinary metabolite was not identified. The NMP concentration in plasma declined in a rapid monoexponential manner, and there was a concomitant increase in the N-oxide concentration. After iv administration of cefepime, which was labeled with 14C in the methyl group of the NMP side chain, 86% of the radiolabel recovered in the urine was attributable to intact antibiotic. The balance was principally present as the N-oxide. Oxidation of NMP to the N-oxide by rat and human liver microsomes was demonstrable in vitro. These results indicate that intravenously administered NMP or NMP arising from the degradation of cefepime in vivo is subject to rapid metabolic clearance.
头孢吡肟（BMY - 28142），7 - [α - （2 - 氨基噻唑 - 4 - 基） - α - （Z） - 甲氧基亚氨基乙酰氨基] - 3 - [（1 - 甲基 - 1 - 吡咯烷基） - 甲基] - 3 - 头孢烯 - 4 - 羧酸是一种强效头孢菌素，其独特之处在于具有季铵化的N - 甲基吡咯烷基侧链。β - 内酰胺环的降解可导致N - 甲基吡咯烷（NMP）释放，N - 甲基吡咯烷是一种脂环族叔胺。静脉推注[甲基 - 14C]NMP后，大鼠和狗尿液中的大部分放射性以极性、不可萃取的代谢物形式存在，该代谢物被分离并鉴定为NMP N - 氧化物。一种次要的尿液代谢物未被鉴定。血浆中NMP浓度以快速单指数方式下降，同时N - 氧化物浓度增加。静脉注射在NMP侧链甲基上标记有14C的头孢吡肟后，尿液中回收的放射性标记物的86%归因于完整的抗生素。其余部分主要以N - 氧化物形式存在。在体外可证明大鼠和人肝微粒体将NMP氧化为N - 氧化物。这些结果表明，静脉注射的NMP或体内头孢吡肟降解产生的NMP会迅速被代谢清除。
